Neurons in the vertebrate central nervous system receive and integrate information from numerous afferent synaptic inputs. Their action potential discharge is a function both of their basic membrane characteristics and the interaction at any given time of specific neurochemical transmitters which alter the membrane conductance properties. The complex organization of the vertebrate CNS and small size of most central neurons limits the use of many contemporary electrophysiological and pharmacological techniques needed to analyze basic membrane properties and mechanisms of transmitter action in vivo. We have developed a model system for the study of the biophysical properties and mechanisms of synaptic integration controlling the activity of defined vertebrate peptidergic neurosecretory cells in the caudal neurosecretory nucleus of fishes. Two electrophysiological approaches are planned. The first will utilize conventional intracellular recording techniques combined with pharmacological treatment to characterize basic membrane properties and to investigate the synaptic response following stimulation of specific afferent inputs. The second aspect will utilize voltage clamp techniques to analyze directly voltage-dependent and transmitter-induced alterations in membrane conductance. The specific aims will be: 1. To establish the basic electrophysiological and pharmacological characteristics of the caudal neurosecretory cells. 2. To analyze the synaptic response produced by stimulation of specific descending inputs and to determine the influence of different antagonists on the synaptic potentials. 3. To characterize the somal membrane ionic conductance systems, and determine the ionic basis of the different synaptic responses using voltage-clamp techiques. 4. To analyze the influence of putative transmitters on the biophysical properties of the somal membrane and compare their response with the physiological response produced by stimulation of specific presynaptic inputs. The results obtained should provide new information about the general membrane properties of neurosecretory cells as well as the mechanisms of synaptic intergration regulating the activity of this neuron type.